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Biomedical subjects

J D Coffman

Publications and source records attributed to J D Coffman.

At least 19 recordsLinked to original sources
PubMed1994

Plasma levels of 5-hydroxytryptamine during sympathetic stimulation and in Raynaud's phenomenon.

1. The involvement of plasma 5-hydroxytryptamine in normal subjects during sympathetic stimulation and in patients with Raynaud's phenomenon was studied. 2. Arterial and venous plasma levels of 5-hydroxytryptamine were measured in normal subjects in a warm room, during reflex sympathetic stimulation by body cooling and during intra-arterial infusions of tyramine. Normal subjects (n = 19) had significantly higher levels of 5-hydroxytryptamine in venous plasma [mean 1.42 (SEM 0.23) ng/ml] than in arterial plasma [0.67 (0.12) ng/ml; P < 0.01]. Body cooling (n = 10) or tyramine infusion (n = 8) did not increase venous levels of 5-hydroxytryptamine despite significant decreases in blood flow and increases in vascular resistance. 3. Venous plasma levels of 5-hydroxytryptamine were also determined in patients with primary Raynaud's phenomenon (n = 12) or secondary Raynaud's phenomenon due to scleroderma (n = 11). Patients with primary or secondary Raynaud's phenomenon did not have significantly higher venous plasma levels of 5-hydroxytryptamine than normal subjects, even during vasospastic attacks (n = 3). 4. It is concluded that either 5-hydroxytryptamine is not involved in sympathetic nerve vasoconstriction or in Raynaud's phenomenon, or 5-hydroxytryptamine released in the microcirculation is largely taken up or metabolized by endothelial cells or platelets.

Adult↗
PubMed1994

Effects of endothelium-derived nitric oxide on skin and digital blood flow in humans.

The effects of NG-monomethyl-L-arginine (L-NMMA) on total finger and forearm, and dorsal finger and forearm skin, blood flows were studied in the basal state and during reflex sympathetic vasoconstriction in normal subjects. Total flows were measured by venous occlusion plethysmography and skin flows by laser-Doppler flowmetry (LDF). L-NMMA in doses of 2, 4, and 8 microM/min given by constant infusion via a brachial artery catheter significantly decreased finger blood flow, forearm blood flow, and vascular conductances. At 8 microM/min, total finger blood flow decreased 38.4% and forearm blood flow decreased 24.8%. Dorsal finger and forearm skin LDF were also significantly decreased (25 and 37% at 8 microM/min). Body cooling significantly decreased finger blood flow (73.6%), vascular conductance, and finger LDF (59.7%). L-NMMA had no effect on total finger blood flow or dorsal finger LDF during body cooling. Nitric oxide or related compounds contribute to the basal dilator tone of the dorsal finger and forearm skin but not during reflex sympathetic vasoconstriction.

Adult↗
PubMed1994

Enhanced cholinergic cutaneous vasodilation in Raynaud's phenomenon.

BACKGROUND: Vasodilator function was determined in patients with Raynaud's phenomenon during intra-arterial infusions of the endothelium-dependent and -independent vasodilators, methacholine and sodium nitroprusside, respectively. Reactive hyperemia, induced by 5 minutes of arterial occlusion with exercise, was also measured. METHODS AND RESULTS: Total blood flow was measured in the fingertip and forearm by venous occlusion plethysmography, and blood flow in the forearm skin was determined with laser Doppler flowmetry. Basal fingertip blood flow was not significantly different between control subjects and patients with Raynaud's phenomenon. Infusions of methacholine had no significant effect on fingertip blood flow in control subjects, whereas patients with Raynaud's phenomenon showed a significant increase in fingertip blood flow. Basal total forearm blood flow was significantly lower in patients with Raynaud's phenomenon than in control subjects. Infusions of methacholine and sodium nitroprusside produced dose-related increases in total forearm blood flow that were of similar magnitudes in the two groups, as were the reactive hyperemic responses. Laser Doppler measurements of forearm skin blood flow, however, showed a significantly greater vasodilator response to methacholine in patients with Raynaud's phenomenon than in control subjects. Infusions of sodium nitroprusside produced a relatively small vasodilator response in the skin of the forearm that was smaller than that to methacholine and not significantly different between the two groups. CONCLUSIONS: In Raynaud's phenomenon, a greater vasodilator response to infusions of methacholine in the fingertip, where changes in blood flow mainly reflect those of skin, and in the skin of the forearm may reflect increased responsiveness of cutaneous blood vessels to stimulation of the endothelium. The mechanism involved is unclear but may result from a general abnormality of blood vessels in the skin, which is related to the pathophysiology of cutaneous vasospasm.

Adult↗
PubMed1993

Chronic inhibition of nitric oxide production augments skin vasoconstriction in the rabbit ear.

The effect of chronic inhibition of nitric oxide (NO) synthesis by NG-nitro-L-arginine methyl ester (L-NAME) on cutaneous ear blood flow (EBF) in the rabbit was examined in vivo with use of laser Doppler flowmetry. Additionally, the efficacy of inhibition of NO by L-NAME was studied ex vivo in isolated preparations of aortic rings from these rabbits. Before surgical implantation of osmotic pumps loaded with L-NAME, resting EBF was not significantly different in rabbits selected for control or L-NAME treatment. Although chronic L-NAME treatment had no significant effect on resting core temperature, resting EBF was reduced significantly in L-NAME-treated rabbits as compared with EBF in control rabbits. Short-term body warming for 10-20 min caused a significant increase in EBF, but not in body temperature, to levels that were not significantly different between groups at 0, 1 and 2 weeks. Prolonged body warming for a further 30-40 min produced a rise in body temperature and a further increase in EBF of 22% to levels that were not significantly different in control and L-NAME-treated groups. Acetylcholine-induced relaxations of aortic rings and levels of cyclic GMP were significantly reduced in L-NAME-treated rabbits as compared with control rabbits, whereas relaxations to sodium nitroprusside were enhanced significantly. These findings demonstrate that the synthesis of NO can be inhibited chronically in the rabbit and are consistent with the concept that NO participates in the control of skin blood flow by counteracting vasoconstrictor tone but not in the vasodilation induced by body warming.

Acetylcholine↗
PubMed1992

Alpha-adrenergic and serotonergic receptors and forearm venous compliance in normal human subjects.

The effect of alpha-adrenergic and serotonergic receptor agonists and antagonists on forearm venous capacitance and vascular resistance was studied in normal subjects. Venous volumes were significantly decreased by phenylephrine, an alpha 1-adrenoceptor agonist, and norepinephrine, which stimulates both alpha 1- and alpha 2-adrenoceptors, but not by the alpha 2-adrenoceptor agonist clonidine. Vascular resistance was increased significantly by all three agonists. Both the alpha 2-adrenoceptor antagonist yohimbine and the alpha 1-adrenoceptor antagonist prazosin attenuated the venoconstrictor and vasoconstrictor response to norepinephrine, indicating that both adrenoceptors are present. 5-Hydroxytryptamine significantly decreased venous volumes, while vascular resistance was not affected. Ketanserin, a 5-HT2 and alpha 1-adrenoceptor antagonist, attenuated the venous volume responses to 5-hydroxytryptamine and phenylephrine. It is concluded that there are alpha 1- and alpha 2-adrenoceptors and 5-HT2 receptors in the forearm venous system. However, vasoactive doses of clonidine are not venoconstricting. Forearm veins are sensitive to doses of 5-hydroxytryptamine, which do not change vascular resistance compared to alpha-adrenoceptor agonists, which affect both.

Adrenergic alpha-Agonists↗
PubMed1991

Raynaud's phenomenon. An update.

The pathogenesis of primary Raynaud's phenomenon remains an enigma. Most evidence favors a local abnormality in the digital arteries as opposed to an increased activity of the sympathetic nervous system. The local fault may involve the alpha 2-adrenergic receptors, which are most important in reflex sympathetic vasoconstriction. Cooling blood vessels increase the sensitivity of alpha 2-adrenergic receptors, increased levels of alpha 2-adrenergic receptors are present in primary Raynaud's disease, and patients show an increased sensitivity to alpha 2-adrenergic receptor agonists on finger blood flow. Serotonin has also been implicated, but the evidence is not compelling. In secondary Raynaud's phenomenon, vasospastic attacks can often be explained by a low arterial distending pressure, a thickened vessel wall, or absence of beta-adrenergic receptor activity. Diagnosis of primary Raynaud's disease relies on a typical history and normal physical examination, laboratory studies, and nailfold capillaroscopy. Finger systolic blood pressures during local cooling with ischemia may be helpful to document vasospastic attacks but does not distinguish primary from secondary Raynaud's phenomenon. The treatment of Raynaud's phenomenon is usually conservative. Pavlovian conditioning or biofeedback may be beneficial. When drug therapy is necessary, the calcium channel entry blocker nifedipine or sympatholytic agents have been shown to decrease the frequency and duration of vasospastic attacks in about two thirds of patients, although subjective improvement does not usually correlate with objective testing. Direct-acting vasodilators have not been shown to be of definite benefit. New therapies include prostaglandins, captopril, and the serotonergic antagonist ketanserin. Surgical sympathectomy has not been beneficial.

Calcium Channel Blockers↗
PubMed1990

Pathogenesis and treatment of Raynaud's phenomenon.

The pathogenetic theories and treatment of Raynaud's phenomenon are reviewed. In primary Raynaud's disease, most evidence supports a local defect at the digital artery level, with vasoconstriction or vasospasm of the digital arteries inducing the color changes. Normal sympathetic activity, low transmural arterial distending forces, and serotonin may be associated factors in the production of vasospastic attacks. In Raynaud's phenomenon, persistent vasoconstriction, thickened vessel walls, increased blood viscosity, and low digital artery blood pressure distal to obstructions may lead to vasospastic attacks with normal sympathetic nerve stimuli. Since the underlying cause of primary Raynaud's disease is unknown, treatment involves the use of agents to reduce sympathetic nerve activity or to prevent vascular smooth muscle contraction. Most patients will respond to conservative measures, but if they fail nifedipine is the drug of choice and alleviates the syndrome in about two thirds of patients. Reserpine and guanethidine may be as effective, but well-controlled studies have not been performed. The beneficial response to prazosin is moderate and dissipates with time. Side effects with these drugs prevent their use in many patients. Diltiazem and nitroglycerin ointments are of questionable value. Ketanserin, a serotonergic S2-receptor antagonist, which has been shown to decrease the frequency of vasospastic attacks, and parenteral prostacyclin are among the new promising therapies.

Animals↗
PubMed1989

International study of ketanserin in Raynaud's phenomenon.

PURPOSE: The effects of ketanserin on primary or secondary Raynaud's phenomenon due to connective tissue disease were studied in a large, international group of patients. PATIENTS AND METHODS: The study population consisted of 222 patients from 10 countries. After a run-in period of one month of placebo therapy, patients were randomly assigned in a double-blind manner to receive ketanserin 40 mg three times daily (n = 113) or placebo (n = 109) for three months. Total finger blood flow was measured in 41 patients in a warm and cool room before and during treatment. Vasospastic episodes were assessed by diaries and global evaluations. RESULTS: A significant reduction of 34% in frequency of episodes occurred with ketanserin, compared to 18% with placebo (p = 0.011). There was a 1% reduction in duration of episodes with ketanserin therapy, compared to a 2% increase with placebo therapy, but this finding was not statistically significant (p = 0.29). No difference was observed in severity of attacks. Global evaluations by investigators (p = 0.03) and patients (p less than 0.01) showed an overall benefit with ketanserin compared to that seen with placebo. Patients with primary or secondary Raynaud's phenomenon responded similarly to treatment. No changes in total finger blood flow were found. CONCLUSION: Ketanserin significantly improves the subjective symptoms of patients with primary or secondary Raynaud's phenomenon and is an appropriate agent to use in this disease when conservative measures fail.

Blood Pressure↗
PubMed1989

Deep venous thrombosis and pulmonary emboli: etiology, medical treatment, and prophylaxis.

Risk factors for venous thrombosis include conditions leading to venous stasis, hypercoagulable states, and trauma to veins. The most important factor is venous stasis. Both extrinsic and intrinsic coagulation pathways are intimately involved in the thrombotic process. In recent years, the importance in thrombus formation of the endothelium, platelet products, the fibrinolytic system, and inhibitors of clotting mechanisms has been discovered. Deficiencies of proteins that normally protect against venous thrombosis have been found. Heparin therapy with subsequent warfarin therapy is still the primary treatment for deep venous thrombosis or pulmonary emboli. Fibrinolytic agents lyse pulmonary emboli but are not as effective in deep venous thrombosis. The incidence of serious bleeding complications has hampered the use of fibrinolytic agents except in emergency situations. Even the newer agents, which act more specifically on thrombi instead of on plasma factors, are associated with a similar incidence of hemorrhagic events. Dextrans are a suitable alternative for treatment of deep venous thrombosis when heparin cannot be used. In the prophylaxis of deep venous thrombosis, minidose heparin (5,000 U every 8 hours subcutaneously) is effective, safe, and convenient in most situations. Heparin-dihydroergotamine, dextran, or warfarin can also be used. Aspirin has been disappointing. In orthopaedic surgery, minidose heparin is not protective; large pulmonary emboli may be prevented by starting warfarin therapy at the time of surgery or by daily dextran infusions. Finally, recent studies have shown that lower doses of warfarin than previously recommended are protective against recurrent venous thrombosis and have a reduced risk of hemorrhagic complications.

Ancrod↗
PubMed1988

New drug therapy in peripheral vascular disease.

New drug therapy for peripheral vascular disease includes the use of nifedipine or sympathetic blocking agents for Raynaud's phenomenon and the use of lower doses of warfarin to prevent recurrence of thromboembolic disease. In prophylaxis of deep venous thrombosis, minidose heparin with or without dihydroergotamine and pneumatic boots are effective. Exercise regimens and the cessation of smoking remain the best therapy for intermittent claudication.

Humans↗
PubMed1988

Role of alpha-adrenoceptor subtypes mediating sympathetic vasoconstriction in human digits.

The effects of intra-arterial administration of alpha-1 and alpha-2 adrenoceptor agonists and antagonists on human digital blood flow were studied before and during reflex sympathetic vasoconstriction in normal subjects. Total finger flow was measured by venous occlusion air plethysmography and capillary flow by the disappearance rate of a radioisotope from a local injection in a fingerpad. Intra-arterial phenylephrine (0.2-1.3 micrograms min-1) and clonidine (0.12-0.48 micrograms min-1) produced dose-related decreases in finger blood flow and increases in vascular resistance. Clonidine was the more potent vasoconstrictor. Prazosin (0.4-3 micrograms min-1) effectively blocked the vasoconstrictor effect of phenylephrine but not clonidine, while yohimbine (30-70 micrograms min-1) blocked the effect of clonidine but not phenylephrine. In a 20 degrees C room, prazosin (0.4-13.2 micrograms min-1) caused no significant changes in finger blood flow (7.7 +/- 2.1 to 11.7 +/- 3.3 ml min-1 100 ml-1) or vascular resistance (30.9 +/- 8.8 to 28.1 +/- 8.7 mmHg ml-1 min-1 100 ml-1). In the 20 degrees C room, yohimbine (30-70 micrograms min-1) produced a significant increase in finger blood flow (7.8 +/- 2.8 to 23.4 +/- 6.8 ml, P less than 0.01) and decrease in vascular resistance (20.5 +/- 5.7 to 6.0 +/- 2.2 units, P less than 0.01). No significant changes occurred in finger capillary flow with prazosin or yohimbine infusions. It is concluded that alpha-1 and alpha-2 adrenoceptors are present in human digital vasculature and that alpha-2 adrenoceptors are more important than alpha-1 adrenoceptors in sympathetic neural vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Serotonergic vasoconstriction in human fingers during reflex sympathetic response to cooling.

The effect on finger blood flow (FBF) of 5-hydroxytryptamine (5-HT) in a 25 degrees C room and the S2-serotonergic receptor antagonist, ketanserin, during reflex sympathetic vasoconstriction was studied in normal subjects. Total FBF was measured by venous occlusion, air plethysmography, and capillary blood flow (FCF) by the disappearance rate of a radioisotope from a fingertip injection. 5-HT in doses of 4 and 8 micrograms/min, given by constant infusion via a brachial artery catheter, significantly decreased FBF [32 +/- (SE) 10.4 to 12.8 +/- 6.6 for 4 micrograms/min and to 5.4 +/- 2.6 ml.min-1.100 ml-1 for 8 micrograms/min, P less than 0.05]. Ketanserin (50 micrograms/min) blocked the vasoconstriction caused by 5-HT. During reflex sympathetic vasoconstriction produced by body cooling, ketanserin increased FBF from 4.1 +/- 1.1 to 39.9 +/- 12.9 ml.min-1.100 ml-1 (P less than 0.025). The vasodilation caused by ketanserin was specific for serotonergic receptors, since it occurred during alpha 1-adrenoceptor blockade with prazosin. Furthermore, the decreases in FBF induced by clonidine and angiotensin II were not significantly different before and during ketanserin infusion. Also, ketanserin further increased FBF after vasodilation of reflexly vasoconstricted fingers by the alpha 2-adrenoceptor antagonist, yohimbine, and phentolamine increased FBF during ketanserin infusions. FCF decreased during 5-HT and increased during ketanserin infusions, demonstrating that both capillary and arteriovenous shunt flow were affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Alpha-adrenergic and serotonergic mechanisms in the human digit.

The effects of intra-arterial administration of alpha 1- and alpha 2-adrenoceptor and S2-serotonergic agonists and antagonists on human digital blood flow were studied before and during reflex sympathetic vasoconstriction caused by body cooling in normal subjects. Total finger blood flow (FBF) was measured by venous occlusion plethysmography and capillary blood flow (FCF) by the disappearance rate of a radioisotope from a local injection in a fingerpad. Intra-arterial phenylephrine and clonidine produced dose-related decreases in FBF and increases in finger vascular resistance (FVR); clonidine was the more potent vasoconstrictor. Prazosin effectively blocked the vasoconstrictor effect of phenylephrine but not clonidine and yet caused no significant change in FBF and FVR during reflex sympathetic vasoconstriction. Yohimbine blocked the effect of clonidine but not phenylephrine and caused a significant increase in FBF and decrease in FVR during vasoconstriction. No significant changes occurred in FCF with prazosin or yohimbine. 5-Hydroxytryptamine decreased FBF and increased FVR. The S2-serotonergic antagonist, ketanserin, blocked the effects of 5-hydroxytryptamine. Ketanserin, in the presence of prazosin, significantly increased FBF and decreased FVR in the reflex vasoconstricted subjects. These studies suggest that both alpha 1- and alpha 2-adrenoceptors are present in the digital vascular bed and that sympathetic nerves control the flow through arteriovenous anastomoses primarily by alpha 2-adrenoceptors. S2-serotonergic receptors are also present in the digital vasculature and may be another important mechanism mediating digital vasoconstriction.

Adult↗
PubMed1988

Pathophysiology of obstructive arterial disease.

Intermittent claudication is due to ischemia of working muscles in patients with stenoses or obstructions of large or medium sized arteries. Arteriosclerosis obliterans is by far the most common etiology. As an arterial stenosis develops, the distal blood flow and blood pressure are not affected until a critical diameter occurs. Then, blood flow and blood pressure fall precipitously with further narrowing of the lumen area. The most important factors that influence blood flow and the blood pressure drop across a stenosis are the radius of the stenosis and of the artery, and the velocity of blood flow. The velocity of blood flow varies inversely with the peripheral resistance. A decrease in peripheral resistance which occurs with exercise, vasodilator drugs, or sympathectomy leads to an increased blood flow velocity and an increased pressure drop across a stenosis. Thus, a non-critical stenosis at rest can become critical and limit blood flow during exercise. In arterial occlusions and critical arterial stenoses, the distal perfusion pressure is decreased due to the high resistance of the small collateral vessels but blood flow may be normal at rest. With exercise, the distal perfusion pressure decreases to a lower level due to the fall in peripheral resistance. Then, the external pressure of muscle contraction may close the arterial bed and stop blood flow. The stimulus to collateral blood vessel development is not known but may involve the pressure differential across the involved vascular bed and metabolic products produced during the ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial Occlusive Diseases↗
PubMed1987

Intra-arterial vasodilator agents to reverse human finger vasoconstriction.

Persistent vasospasm of the digits is difficult to attenuate or reverse. We studied the effect of intra-arterial nitroprusside on humoral and neurogenic digital vasoconstriction. Fingertip blood flow (FBF) was measured by venous occlusion plethysmography and capillary flow (CF) by the disappearance rate of a local injection of radioisotope. Small doses of nitroprusside (1 to 2 micrograms/min) increased FBF in fingers vasoconstricted by intra-arterial norepinephrine (4.7 +/- SE 1.7 to 38.4 +/- 26 ml min-1 100 ml-1 of tissue). Large doses of nitroprusside (up to 40 micrograms/min) did not increase FBF (11.8 +/- 6.0 ml to 6.6 +/- 3.9 ml) in fingers vasoconstricted by sympathetic nerve stimulation (body cooling). Forearm blood flow was measured in six subjects in the cool room and all showed an increase in flow with nitroprusside (6.7 +/- 1.1 ml to 26.0 +/- 6.0 ml), demonstrating that effective doses were used. Nitroglycerin (2.5 to 5 micrograms/min) significantly increased FBF from 5.1 +/- 1.9 ml to 14.8 +/- 6.9 ml as did phentolamine (50 to 100 micrograms/min) from 6.7 +/- 2.8 ml to 36.0 +/- 11.3 ml in sympathetically vasoconstricted subjects. Only phentolamine increased CF significantly (0.8 +/- 0.2 ml to 2.8 +/- 0.6 ml). Nitroprusside is an effective vasodilator for humorally induced vasoconstriction, but sympathetic digital vasoconstriction is resistant to nitroprusside and nitroglycerin is less effective than phentolamine. Phentolamine is the preferred agent because it increased FBF and CF.

Female↗